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Olivier Dulac

Publications and source records attributed to Olivier Dulac.

At least 19 recordsLinked to original sources
PubMed2006

Herpes simplex virus encephalitis in human UNC-93B deficiency.

Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of sporadic viral encephalitis in western countries. Its pathogenesis remains unclear, as it affects otherwise healthy patients and only a small minority of HSV-1-infected individuals. Here, we elucidate a genetic etiology for HSE in two children with autosomal recessive deficiency in the intracellular protein UNC-93B, resulting in impaired cellular interferon-alpha/beta and -lambda antiviral responses. HSE can result from a single-gene immunodeficiency that does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies. Other severe infectious diseases may also reflect monogenic disorders of immunity.

Child, Preschool↗
PubMed2006

How children suffering severe amnesic syndrome acquire new concepts?

Recent studies revealed that children with developmental amnesia acquired new semantic information. However, they failed to investigate the growth of such knowledge during childhood, and they did not bring evidence concerning the putative role of residual episodic memory in semantic acquisition. This prospective study sought to clarify this issue by assessing both semantic and episodic memory in two amnesic children (RH and KF) with different neuropsychological profiles. We thus applied errorless semantic learning and vanishing cues methods, together with assessments of episodic memory using original recognition tasks within the same protocol. Results demonstrated learning and long-lasting maintenance of multicomponent concepts (comprising labels, categories and features) in both amnesic children. Importantly, episodic memory assessments revealed differential residual abilities in these children, which may account for their respective profiles of semantic acquisition. Thus, RH, who demonstrated residual episodic abilities, acquired normally. However, the learning of KF, who had a massive impairment of episodic memory, remained slower than her controls. In conclusion, even though an episodic impairment may slacken new semantic learning, our research provides new evidence for the de novo acquisition of semantic concepts in childhood amnesic syndrome and strengthens the idea that semantic learning can occur without any recruitment of episodic memory.

Amnesia↗
PubMed2006

Delineation of the motor disorder of Lesch-Nyhan disease.

Lesch-Nyhan disease (LND) is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit over-production of uric acid, along with a characteristic neurobehavioural syndrome that includes mental retardation, recurrent self-injurious behaviour and motor disability. Prior studies involving relatively small numbers of patients have provided different conclusions on the nature of the motor disorder. The current study includes the results of a multi-centre international prospective study of the motor disorder in the largest cohort of patients studied to date. A total of 44 patients ranging from 2 to 38 years presented a characteristic motor syndrome that involved severe action dystonia superimposed on baseline hypotonia. Although some patients also displayed other extrapyramidal or pyramidal signs, these were always less prominent than dystonia. These results are compared with a comprehensive review of 122 prior reports that included a total of 254 patients. Explanations for the differing observations available in the literature are provided, along with a summary of how the motor disorder of LND relates to current understanding of its pathophysiology involving the basal ganglia.

Adolescent↗
PubMed2006

Evaluation of CACNA1H in European patients with childhood absence epilepsy.

CACNA1H was evaluated in a resource of Caucasian European patients with childhood absence epilepsy by linkage analysis and typing of sequence variants previously identified in Chinese patients. Linkage analysis of 44 pedigrees provided no evidence for a locus in the CACNA1H region and none of the Chinese variants were found in 220 unrelated patients.

Asian People↗
PubMed2006

Misleading effects of clonazepam in symptomatic electrical status epilepticus during sleep syndrome.

Electrical status epilepticus during sleep syndrome and its variants are age-dependent epileptic encephalopathies associated with a sleep-related electroencephalographic pattern of continuous spike-waves, combined with motor or cognitive impairment. These epileptic encephalopathies are usually not responsive to conventional antiepileptic drugs. This report describes two children in whom clonazepam had no effect on cognitive and motor disorders but controlled spike activity, preventing a proper diagnosis. Withdrawal of clonazepam was accompanied by the recurrence of continuous spike-waves in slow sleep, permitting the diagnosis of electrical status epilepticus during sleep syndrome and appropriate therapeutic decisions. These two cases of the misleading effect of clonazepam in electrical status epilepticus during sleep syndrome illustrate the puzzling situation that can occur when therapeutic options only consider the electroencephalographic features without prior syndromic diagnosis.

Anticonvulsants↗
PubMed2006

Severe memory impairment in a child with bihippocampal injury after status epilepticus.

Epilepsy may contribute to memory deficits in children, but these deficits are generally mild. We describe the neuropsychological profile of a female who had prolonged status epilepticus at 5 years of age, and then developed temporal lobe epilepsy. Brain magnetic resonance imaging 1 month after the onset of status epilepticus showed marked bilateral hippocampal atrophy that seemed disproportionate to the mild cortico-subcortical atrophy. At the age of 7 years, this child had cognitive impairment (an IQ of 62), which particularly affected her memory. This included short-term memory, and immediate and delayed memory deficits for verbal and visual materials that had a profound impact on everyday life. This observation demonstrates that severe status epilepticus can cause predominant bilateral hippocampal atrophy in childhood. In contrast with children who develop such damage after anoxia, this may result in general cognitive impairment but also in more severe episodic memory deficit.

Atrophy↗
PubMed2006

Epilepsy in Menkes disease: analysis of clinical stages.

PURPOSE: Epilepsy is one of the main features of Menkes disease (MD), although it is not described in depth. To determine the spectrum of epilepsy, we studied its main characteristics. METHODS: Based on clinical charts, we retrospectively analyzed the evolution of electroclinical features of 12 patients with confirmed MD. RESULTS: Epilepsy could be divided into three periods: (a) an early stage (median age, 3 months), characterized by focal clonic status epilepticus, usually triggered by fever (10 patients). Ictal EEG showed runs of slow spike-waves and slow waves in the posterior regions, and interictal EEG multifocal and polymorphic slow waves (three cases), or mixed slow spike-waves and slow waves (seven cases). Partial seizure control was obtained in nine patients during 5.9 months; (b) an intermediate stage (median age, 10 months) with intractable infantile spasms (11 patients) in which interictal EEG demonstrated modified hypsarrhythmia (seven cases), diffuse irregular slow waves and spike-waves (four cases). Six patients died at the median age of 15 months; and (c) a late stage in the six remaining patients (median age, 25 months), with multifocal seizures, tonic spasms, and myoclonus in four patients, whereas two patients became seizure free. Interictal EEG showed multifocal high-amplitude activity, mixed with irregular slow waves in all six cases. These patients died at the median age of 3.6 years. CONCLUSIONS: Based on a relatively large series of MD patients with a quite prolonged survival, we individualized three successive periods in the course of epilepsy: early focal status, then infantile spasms, and then myoclonic and multifocal epilepsy after age 2 years.

Adult↗
PubMed2006

Early pattern of epilepsy in the ring chromosome 20 syndrome.

PURPOSE: The characteristics of epilepsy in ring chromosome 20 have been reported in adolescents and adults. The mode of onset most often remains imprecise. To clarify this onset period, we studied the early-onset features in our personal series and in the reported pediatric cases. METHODS: Our series comprises one child with an onset of epilepsy in the neonatal period and five others with an onset before age 8 years. The cases in the literature with an epilepsy onset before 8 years also were reviewed. RESULTS: Seizures in the neonatal period were described as motor seizures. Our personal patient with a neonatal onset had severe psychomotor delay. In both infancy and early childhood, the EEG showed no interictal frontal localization of the anomalies, and no long-lasting seizure was recorded. Seizures with terror and hallucinations usually appeared from about age 4 years. It is not before the age of 8 years that the usual interictal EEG pattern appeared of rhythmic theta slow-waves activity with spikes predominating in frontal areas described in adolescence and adulthood. The interictal EEG showed 1- to 2-Hz delta slow waves and spike-and-waves predominating in frontal areas, but no physiologic activity. CONCLUSIONS: In ring 20 chromosome, specific epilepsy features are lacking in the neonate, but the whole phenotype shows a more severe expression in terms of mental delay. The characteristic frontal EEG pattern and ictal terror do not appear before age 4 to 5 years.

Adolescent↗
PubMed2006

Cryptogenic late-onset epileptic spasms: an overlooked syndrome of early childhood?

PURPOSE: Few reports detailing late-onset epileptic spasms have been published. To determine whether this condition merely represents a late variant of classic West syndrome or exhibits specific features distinct from the latter and related to a later stage of brain maturation, we analyzed the whole population with this specific seizure type, excluding symptomatic cases to avoid the effect of brain lesion. METHODS: We reviewed the files of the 56 children evaluated for epileptic spasms in clusters having begun at age 12 months or later and analyzed clinical and video-EEG data of the 22 patients (4-17 years; mean, 8.5 years) without obvious cause. RESULTS: Interictal EEG did not show classic hypsarrhythmia. A temporal or temporofrontal slow wave and/or spike focus could be identified in all cases. Twelve children showed spasms with a tonic component. Ictal EEG revealed generalized high-voltage slow wave followed by diffuse voltage attenuation with superimposed fast activity. All children also exhibited other types of recorded seizures consisting of bursts of spike-waves with temporofrontal predominance, reminiscent of "atypical absences." In contrast with the occurrence of tonic components within a cluster of spasms, no tonic seizure stricto sensu was recorded or reported by the caregivers. In 10 children, treatment (two vigabatrin, seven hydrocortisone, one adrenocorticotropic hormone) achieved complete cessation of seizures and disappearance of focal EEG anomalies, but spasms persisted in 12 children. CONCLUSIONS: The cryptogenic group in our series without recognized cause and temporal or temporofrontal EEG anomalies seems to represent a type of epileptic encephalopathy intermediary between West and Lennox-Gastaut syndromes, in terms of seizure types and interictal EEG, and could correspond to dysfunction of the maturation process of the temporal lobe, possibly due to an undisclosed lesion.

Adolescent↗
PubMed2006

Linkage analysis and disease models in benign familial infantile seizures: a study of 16 families.

PURPOSE: Benign familial infantile seizures (BFIS) is a genetically heterogeneous condition characterized by partial seizures, onset age from 3 to 9 months, and favorable outcome. BFIS loci were identified on chromosomes 19q12-13.1 and 16p12-q12, allelic to infantile convulsions and choreathetosis. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS may show overlapping clinical features. Infantile seizures also were in a family with familial hemiplegic migraine and mutations in the ATP1A2 gene. We have examined the heterogeneous genetics of BFIS by means of linkage analysis. METHODS: Sixteen families were examined. Probands underwent neurologic examination, at least one EEG recording, and, when possible, brain CT and MRI. Clinical information about relatives was collected. Families with SCN2A or ATP1A2 mutations were excluded from the study. Chromosome 16p and 19q loci were examined by linkage analysis using two models that differed in penetrance rate. Genetic heterogeneity was evaluated with both models. RESULTS: Clinical information was available for 124 members of affected families. BFIS was diagnosed in 69 subjects. One patient without BFIS had a single febrile seizure, and another had rare episodes of paroxysmal dystonia. Evidence of linkage was obtained only for chromosome 16. Moreover, the high penetrance allowed the identification of genetic heterogeneity. CONCLUSIONS: Our data confirm the relevance of the chromosome 16 locus in BFIS and suggest the presence of an additional locus. This study shows that the genetic model used affects the outcome of linkage analysis.

Brain↗
PubMed2006

Epilepsy as a consequence of cerebral malaria in area in which malaria is endemic in Mali, West Africa.

PURPOSE: Cerebral malaria (CM) is suspected to be a potential cause of epilepsy in tropical areas, but little information is available. The purpose of this study was to evaluate the role of CM in epilepsy among children in Mali. METHODS: An exposed-nonexposed study was performed to identify children who had epilepsy after malaria in the 0- to 15-year age group. The exposure factor was CM defined according to World Health Organization (WHO) criteria, and the nonexposure factor was symptomatic malaria without the characteristics of CM (NCM). All the children underwent a screening questionnaire and were examined by a medical physician. After the screening phase, a specialist in neuropediatrics examined the children suspected to have epilepsy. EEG and computed tomography (CT) scans were performed in some of these patients. RESULTS: In total, 101 subjects who had had CM and 222 who had had NCM were included. Fifty-four children (CM, 34; NCM, 20) were suspected to have epilepsy, and six were confirmed (CM, five; NCM, one). The incidence rate was 17.0 per 1000 person-years in the CM group and 1.8 per 1000 person-year in the NCM group; thus the relative risk (RR) was 9.4 [95% confidence interval (CI), 1.3-80.3; p = 0.02]. After adjustment on age and duration of follow-up, the RR was 14.3 (95% CI, 1.6-132.0; p = 0.01). CONCLUSIONS: The risk of sequelar epilepsy is significantly higher in the CM group compared with the NCM group. A reevaluation of this cohort should be carried out later to search for temporal epilepsy that appeared after age 10 years.

Age Factors↗
PubMed2006

Exploration of the genetic architecture of idiopathic generalized epilepsies.

PURPOSE: Idiopathic generalized epilepsy (IGE) accounts for approximately 20% of all epilepsies and affects about 0.2% of the general population. The etiology of IGE is genetically determined, but the complex pattern of inheritance suggests an involvement of a large number of susceptibility genes. The objective of the present study was to explore the genetic architecture of common IGE syndromes and to dissect out susceptibility loci predisposing to absence or myoclonic seizures. METHODS: Genome-wide linkage scans were performed in 126 IGE-multiplex families of European origin ascertained through a proband with idiopathic absence epilepsy or juvenile myoclonic epilepsy. Each family had at least two siblings affected by IGE. To search for seizure type-related susceptibility loci, linkage analyses were carried out in family subgroups segregating either typical absence seizures or myoclonic and generalized tonic-clonic seizures on awakening. RESULTS: Nonparametric linkage scans revealed evidence for complex and heterogeneous genetic architectures involving linkage signals at 5q34, 6p12, 11q13, 13q22-q31, and 19q13. The signal patterns differed in their composition, depending on the predominant seizure type in the families. CONCLUSIONS: Our results are consistent with heterogeneous configurations of susceptibility loci associated with different IGE subtypes. Genetic determinants on 11q13 and 13q22-q31 seem to predispose preferentially to absence seizures, whereas loci on 5q34, 6p12, and 19q13 confer susceptibility to myoclonic and generalized tonic-clonic seizures on awakening.

Chromosome Mapping↗
PubMed2006

Stiripentol in childhood partial epilepsy: randomized placebo-controlled trial with enrichment and withdrawal design.

Stiripentol, a new antiepileptic drug inhibiting cytochrome P450-enzymes, suggested some efficacy when combined with carbamazepine in an open trial in refractory partial epilepsy of childhood. Our objective was to test these results in a placebo-controlled trial. To limit the number of patients included, we used an enrichment and withdrawal design. Among the 67 children entered in a 4-month open add-on stiripentol study following a 1-month single-blind placebo baseline, the 32 responders were randomized for 2 months either to continue stiripentol (n = 17) or to withdraw to placebo (n = 15). If seizures increased by at least 50% after randomization compared with baseline, the patients dropped out (primary end point): there were six patients on stiripentol and eight patients on placebo (not significant). However, a decrease in seizure frequency compared with baseline (secondary end point) was greater on stiripentol (-75%) than on placebo (-22%) (P < .025). Twelve patients experienced at least one adverse event on stiripentol (71%) compared with four patients on placebo (27%); none were reported as severe. The combination of stiripentol and carbamazepine proved to reduce seizure frequency in children with refractory partial epilepsy, although it failed to show a significant impact according to the escape criteria selected as the primary end point in the present study, for ethical reasons.

Adolescent↗
PubMed2005

Deficit of preparatory attention in children with frontal lobe epilepsy.

We compared the performance of a sustained attention task by children with epilepsy in either the frontal or temporal lobe. In a new simple task that specifically measures preparatory attention, developed recently by LaBerge, Auclair, and Siéroff [LaBerge, D., Auclair, L., & Siéroff, E. (2000). Preparatory attention: Experiment and theory. Consciousness and Cognition, 9, 396-434], patients responded to a target presented in the centre of the display and ignored a distracter presented at locations to the right or the left side of the target. The distracter was presented prior to the onset of the target and the relative frequency of the distracter to target was varied within a block of trials (from 0% to 67%). Children with frontal lobe epilepsy showed a higher mean slope of response time to the target as a function of distracter probability compared to children with temporal lobe epilepsy or compared to the response time slope of control subjects. The response time slope of children with temporal lobe epilepsy did not differ from that of control subjects. These results indicate that the presence of frontal lobe epilepsy selectively affects the capacity of these patients to resist the interference a distracter.

Adolescent↗
PubMed2005

Atypical case of hemiconvulsions-hemiplegia-epilepsy syndrome revealing contralateral focal cortical dysplasia.

Hemiconvulsions-hemiplegia-epilepsy syndrome (HH/HHE) is a rare epileptic syndrome consisting of a prolonged unilateral convulsion producing a persisting hemiplegia, sometimes followed by epilepsy. We report on a 13-month-old male who presented with febrile left-sided HH syndrome with right hemispheric unilateral cytotoxic oedema followed by hemispheric atrophy on magnetic resonance imaging (MRI). Six months later the child progressively developed refractory focal epilepsy, including right hemiclonic seizures, and nearly continuous left frontal rhythmic spikes, suggesting the presence of a focal cortical dysplasia (FCD). A repeat MRI at 2 years of age showed left frontal FCD. This unusual case of dual pathology--right HH syndrome and left FCD--suggests that some other factor than the malformation determined the prolonged status and brain atrophy. The kinetics of regional cortical maturation could explain this unusual condition.

Brain Diseases↗
PubMed2005

Monozygotic twins discordant for epilepsy differ in the levels of potentially pathogenic autoantibodies and cytokines.

Can autoantibodies (Ab's) and cytokines play a role in epilepsy?Monozygotic twins discordant for epilepsy (most probably Rasmussen's encephalitis (RE)), compared to 49 neurologically intact controls, were both found to contain in their serum (at the time of epilepsy diagnosis) significantly elevated levels of specific Ab's against peptide B (amino acids 372-395) of the ionotropic glutamate receptor of AMPA subtype 3 (i.e. GluR3B peptide). Interestingly, both twins also had clinically elevated levels of Ab's to double-stranded (ds) DNA, glutamic acid decarboxylase, nuclear antigens, beta2-glycoprotein I and cardiolipin, as in "classical" autoimmune diseases. Both twins also had significantly elevated levels of IFNgamma, TNFalpha, IL-4 and IL-10 in the serum, compared to the controls. Comparing the twins revealed that the epileptic twin had significantly higher levels of five of the above anti-self Ab's, but significantly lower levels of all four cytokines compared to her healthy sister. Importantly, the epileptic twin, alike three other RE patients tested herein, contained elevated levels of Ab's to GluR3B and dsDNA also in cerebrospinal fluid (CSF) (unavailable of the healthy twin). Our results suggest that the various autoimmune Ab's studied herein, all of which are known already to have a potential to be pathogenic in the nervous system and/or peripheral organs, may play a role in some types of epilepsy. The titer of such Ab's and of key cytokines may be crucial for either facilitating or arresting the development of epilepsy. Our findings also show that anti-GluR3B Ab's in serum are not necessarily detrimental (their presence in the CSF may be more dangerous), and that they are not a mere side effect of already existing epilepsy, as they were found herein in serum of a healthy individual. These findings and suggestions may be of clinical importance and call for further studies.

Autoantibodies↗
PubMed2005

Bioequivalence of a new sustained-release formulation of sodium valproate, valproate modified-release granules, compared with existing sustained-release formulations after once- or twice-daily administration.

STUDY OBJECTIVE: To compare the pharmacokinetic properties of valproate modified-release (MR) granules with those of two existing valproate sustained-release (SR) formulations to confirm their bioequivalence. DESIGN: Two randomized, open-label, two-period crossover studies under fasting conditions, and one open-label, randomized, single-dose, three-period crossover study under fasting and nonfasting conditions. Each study had a 7-day washout interval between periods. SETTING: Three hospitals in France. SUBJECTS: Healthy male Caucasian volunteers aged 18-35 years (27 subjects in study 1, 24 in study 2, and 24 in study 3). INTERVENTION: In studies 1 and 2, during two 15-day periods, subjects received either valproate MR granules or an existing valproate SR formulation. In study 3, subjects received only valproate MR granules 500 mg, once with water after a 10-hour fast, once with yogurt after a 10-hour fast, and once 30 minutes after a high-fat morning meal. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected, and pharmacokinetic parameters of valproic acid were determined for single-dose (studies 1-3) and repeated-dose (studies 1 and 2) administration. The 90% confidence intervals (CIs) for area under the concentration-time curve and maximum concentration (C max ) were in the acceptance limits for bioequivalence (i.e., 90% CI 0.80-1.25) after single and repeated doses of valproate MR granules administered once/day or twice/day. Although time to C max was slightly decreased with valproate MR granules, this difference did not induce a significant difference in terms of C max . Valproate MR granule formulation was bioequivalent with existing SR formulations. High-fat breakfast or yogurt did not modify either the bioavailability or pharmacokinetic profile of valproate MR granules. This formulation was well tolerated. The adverse event profile did not differ among the various regimens. CONCLUSION: Valproate MR granules, administered once/day or twice/day, may be an attractive alternative to existing SR formulations for patients who have difficulties with swallowing tablets or who favor granules over tablets.

Adult↗